The skin is the primary barrier protecting other organs and internal tissues from the external environment. Epicutaneous application of some environmental chemicals results in a T cell- mediated inflammatory response termed allergic contact dermatitis or contact hypersensitivity (CHS). Most studies examining the immmunpathogenesis of allergic contact dermatitis have focused on the induction phase of the response. Much less is known about the cellular and molecular requirements for elicitation of allergic contact dermatitis once sensitization has occurred. In this proposal, we hypothesize that: the requirement of antigen presenting cells and the costimulatory molecules that they express for induction and elicitation of CHS reactions are different. We will examine this issue in mice by assessing the types of cells that can serve as antigen presenting cells for elicitation of the response. MHC class I and class II antigens that are known to be important for induction of allergic contact dermatitis will be examined for their role during the elicitation phase of the response. Based on our preliminary data indicating that transfer of hapten primed T cells to ICAM-1 deficient mice elicited a reduced CHS response and the development of hapten primed T cells in the mice was impaired, the role of ICAM-1 in the elicitation of CHS will be determined. We will also evaluate whether those antigen-presenting cells that are unable to elicit CHS have the capacity to desensitize animals that have already been sensitized to hapten. Because our current results indicate that CHS is significantly increased in gammadeltaT cell deficient mice, the potential regulatory effects of gammadeltaT cells will also be evaluated. On a basic level, the results will provide new information concerning the pathogenesis of allergic contact dermatitis and interactions between the skin and the immune system. On a clinical level, the information should be useful for the development of new specific strategies for the prevention and treatment of this common skin disease.
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